| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| ln Vitro |
At IC50 values of less than 0.5 nM and 2.9 nM, respectively, CPI-1612 inhibits both full-length EP300 and full-length CBP [1]. CPI-1612 has IC50 values of 14 nM and <7.9 nM, respectively, which suppress the growth of JEKO-1 cells and H3K18Ac MSD (H3K18=histone 3 lysine 18, MSD=mesoscale discovery)[1]. CYP2C8 (IC50=1.9 μM) and CYP2C19 (IC50=2.7 μM) are moderately inhibited by CPI-1612 (Compound 17), but its action in the hERG binding assay is weak (IC50=10.4 μM) [1].
Inhibits H3K18Ac MSD (IC50 = 14 nM) and JEKO-1 cell proliferation (IC50 <7.9 nM). Weak hERG binding (IC50 = 10.4 uM); moderate CYP2C8 (1.9 uM) and CYP2C19 (2.7 uM) inhibition. Highly brain-penetrant (brain-to-plasma ratio 0.35). |
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| ln Vivo |
CPI-1612 (Compound 17; 0.5 mg/kg; buffered solution; twice daily; for 4 weeks) decreased H3K27Ac in the buffer and H3K18Ac in the tumor, hence preventing tumor development by 67% [1]. Compound 17 (1612) administered intravenously at a dose of 0.5 mg/kg; 1.0 mg/kg border clearance = 0.42 L/h/kg, Vss = 3.7 L/kg, T1/2 = 5.5 h, F% = 71; AUC/Dose = 1691 h·mg/mL) and mice (1 mg/kg i.v.; 5 mg/kg Boundary clearance = 3.8 L/h/kg, Vss = 2.0 L/kg, T1/2 = 0.98 h, F % = 79; AUC/dose = 211 h·mg/mL)[1]. CD-1 mice were given a single dose of CPI-1612, and the durations of their venous and cerebral exposure to the drug were recorded at 0.25, 0.5, 1.0, 2.0, 4.0, and 8.0. CPI-1612 has a single post-lateral wall-to-cerebrovascular ratio of 0.35, indicating that it is extremely brain-penetrating[1].
In C57B6 JEKO-1 xenograft mice, oral CPI-1612 (0.5 mg/kg, BID, 4 weeks) achieves 67% TGI with reduced H3K27Ac and H3K18Ac. Good PK in dogs (F%=71) and mice (F%=79); rat oral exposure limited (F%=9). Highly brain-penetrant (0.35 brain/plasma ratio). |
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| Enzyme Assay |
EP300 HAT inhibitory activity measured using a homogeneous time-resolved fluorescence (HTRF) assay with recombinant EP300, biotinylated histone H3 peptide, and acetyl-CoA. IC50 determined by detecting acetylated product formation.
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| Cell Assay |
JEKO-1 lymphoma cells (or ER+ breast cancer cells) cultured with increasing CPI-1612 doses (0-10 uM) for 72-96h. Cell viability measured by CellTiter-Glo (ATP quantitation). H3K18Ac MSD assay used to assess target engagement in cells.
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| Animal Protocol |
Animal/Disease Models: C57B6 mice injected with JEKO- 1 cell [1]
Doses: 0.5 mg/kg Doses: po (po (oral gavage)) twice (two times) daily; for 4 weeks Experimental Results: 67% tumor growth inhibition at 0.5 mg/kg dose (TGI). JEKO-1 xenograft in C57B6 mice. Mice implanted subcutaneously with cells; when tumors reach ~100-200 mm3, mice receive CPI-1612 0.5 mg/kg PO BID for 4 weeks. Tumor volume measured twice weekly; endpoint TGI calculated and tissues collected for pharmacodynamic analysis (H3K18Ac, H3K27Ac). |
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| ADME/Pharmacokinetics |
Dog (0.5 mg/kg IV; 1 mg/kg PO): CL = 0.42 L/h/kg, Vss = 3.7 L/kg, T1/2 = 5.5 h, F% = 71. Mouse (1 mg/kg IV; 5 mg/kg PO): CL = 3.8 L/h/kg, Vss = 2.0 L/kg, T1/2 = 0.98 h, F% = 79. Rat (1 mg/kg IV; 5 mg/kg PO): CL = 2.6 L/h/kg, Vss = 1.8 L/kg, T1/2 = 1.2 h, F% = 9.
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| Toxicity/Toxicokinetics |
Weak hERG activity (IC50 = 10.4 uM) suggests low cardiac risk. Moderate CYP inhibition (2C8 IC50 1.9 uM; 2C19 IC50 2.7 uM) may indicate potential drug-drug interactions. No severe toxicity reported at 0.5 mg/kg BID in mice.
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| References | ||
| Additional Infomation |
Discovered by Cellcentric Inc. (CPI). First disclosed in ACS Med Chem Lett 2020 (Wilson et al.). Phase I clinical trials may be ongoing; currently a research tool for EP300/CBP biology, especially in oncology (breast cancer, lymphoma) and neurological diseases where EP300/CBP dysregulation is implicated.
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| Molecular Formula |
C27H26N6O
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|---|---|
| Molecular Weight |
450.534945011139
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| Exact Mass |
450.216
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| CAS # |
2374971-81-8
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| Related CAS # |
(R,R)-CPI-1612;2374972-35-5;(S,S)-CPI-1612;2374971-82-9
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| PubChem CID |
146014965
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
693
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C([C@@H](C1C=CC=CC=1)NC[C@@H](C)C1C=CC(C#N)=CC=1)NC1C=CC(=CN=1)C1C=NN(C)C=1
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| InChi Key |
SEDFZSHSBUXKAC-NIYFSFCBSA-N
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| InChi Code |
InChI=1S/C27H26N6O/c1-19(21-10-8-20(14-28)9-11-21)15-30-26(22-6-4-3-5-7-22)27(34)32-25-13-12-23(16-29-25)24-17-31-33(2)18-24/h3-13,16-19,26,30H,15H2,1-2H3,(H,29,32,34)/t19-,26-/m1/s1
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| Chemical Name |
(2R)-2-[[(2S)-2-(4-cyanophenyl)propyl]amino]-N-[5-(1-methylpyrazol-4-yl)pyridin-2-yl]-2-phenylacetamide
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| Synonyms |
P300/CBPIN6 P300/CBP IN 6CPI-1612 CPI1612 CPI 1612
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~230 mg/mL (~510.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (11.10 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (11.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2196 mL | 11.0980 mL | 22.1961 mL | |
| 5 mM | 0.4439 mL | 2.2196 mL | 4.4392 mL | |
| 10 mM | 0.2220 mL | 1.1098 mL | 2.2196 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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